Cancer in experimental animals exposed to arsenic and arsenic compounds.

Inorganic arsenic is a ubiquitous environmental contaminant that has long been considered a human carcinogen. Recent studies raise further concern about the metalloid as a major, naturally occurring carcinogen in the environment. However, during this same period it has proven difficult to provide experimental evidence of the carcinogenicity of inorganic arsenic in laboratory animals and, until recently, there was considered to be a lack of clear evidence for carcinogenicity of any arsenical in animals. More recent work with arsenical methylation metabolites and early life exposures to inorganic arsenic has now provided evidence of carcinogenicity in rodents. Given that tens of millions of people worldwide are exposed to potentially unhealthy levels of environmental arsenic, in vivo rodent models of arsenic carcinogenesis are a clear necessity for resolving critical issues, such as mechanisms of action, target tissue specificity, and sensitive subpopulations, and in developing strategies to reduce cancers in exposed human populations. This work reviews the available rodent studies considered relevant to carcinogenic assessment of arsenicals, taking advantage of the most recent review by the International Agency for Research on Cancer (IARC) that has not yet appeared as a full monograph but has been summarized (IARC, 2009 , IARC Special Report: Policy, Vol. 10. Lyon: IARC Press, 453­454). Many valid studies show that arsenic can interact with other carcinogens/agents to enhance oncogenesis, and help elucidate mechanisms, and these too are summarized in this review. Finally, this body of rodent work is discussed in light of its impact on mechanisms and in the context of the persistent argument that arsenic is not carcinogenic in animals.

Optimizing selection of patients for major lung resection.

OBJECTIVES: It is not known whether a normal diffusing capacity for carbon monoxide permits safe lung resection in patients with marginal spirometric values, or whether normal spirometric values negate the adverse effects of a low diffusing capacity. The purposes of this study were (1) to determine the best predictors of morbidity and mortality and (2) to assess whether interactions exist between diffusing capacity and spirometry that help estimate outcome after major lung resection. DESIGN: A retrospective analysis of 376 patients who underwent lung resection was performed. Three hundred three had lung cancer and 73 had other disease. Two hundred eighty-four underwent lobectomy/bilobectomy and 92 had pneumonectomy. We assessed the relationship of 23 preoperative variables to 18 postoperative events classified into categories as pulmonary or cardiac complications, overall morbidity, and operative mortality. RESULTS: The best single predictor of complications was the percent predicted postoperative diffusing capacity. The incidences of pulmonary and cardiac complications, morbidity, and mortality were inversely related to predicted postoperative diffusing capacity percent (p < 0.004 for each). Multivariate logistic regression analyses identified only predicted postoperative diffusing capacity percent and age as significant independent predictors of pulmonary complications, morbidity, and death, and these with prior myocardial infarction predicted cardiac complications. There were no interactions between percent predicted postoperative forced expiratory volume in 1 second and predicted postoperative diffusing capacity percent in estimating risks of complications. CONCLUSION: Predicted postoperative diffusing capacity percent is the strongest single predictor of risk of complications and mortality after lung resection. There is little interrelationship of predicted postoperative diffusing capacity percent and predicted postoperative forced expiratory volume in 1 second, indicating that these values should be assessed independently in estimating operative risk.

Results of myotomy and partial fundoplication after pneumatic dilation for achalasia.

BACKGROUND: We questioned whether results of myotomy for achalasia are influenced by previous pneumatic dilation and whether surgical outcome is influenced by a dilation-related perforation necessitating urgent operation. METHODS: We performed a retrospective analysis of 60 patients who underwent transthoracic myotomy and fundoplication from 1977 to 1995. Dysphagia, heartburn, pain, and regurgitation were scored on a scale of 0 to 3 and results were classified according to combined symptom score. RESULTS: Dilation was performed before myotomy once in 15 patients, twice in 25, 3 times or more in 9, and never in 11 patients. Operation was urgent due to perforation in 6 patients (10%). There was no postoperative leak or mortality. Overall symptom score at last follow-up (57 +/- 8 months; 90% of patients) was improved compared with preoperative score (2.1 +/- 0.3 months versus 5.1 +/- 0.2 months; p < 0.0001). Outcome was unrelated to whether or not a perforation occurred (excellent/good outcomes in 100% and 88%, respectively) or to whether or not preoperative dilations had been performed (excellent/good outcomes in 90% and 89%, respectively). CONCLUSIONS: Myotomy and partial fundoplication is an effective technique for management of achalasia. Results are unaffected by the need for urgent operation for perforation and are unrelated to whether pneumatic dilation is performed preoperatively.

Recurrent spontaneous perforation of the esophagus.

Boerhaave's syndrome is uncommon and its precise etiology is unclear. Information regarding the long-term outcome of patients surviving this injury is lacking. We present the case of a patient who suffered two spontaneous perforations of the esophagus that occurred 30 years apart.

Esophagectomy in the septuagenarian.

As the population continues to age, older patients are being referred for thoracic surgical procedures with increasing frequency. From 1985 through 1992, 38 patients (32 men, 6 women) 70 years of age or older underwent esophagectomy for primary esophageal carcinoma. Histologic findings included adenocarcinoma in 28 (74%) and squamous carcinoma in 10 (26%). Patients suffered dysphagia for a mean of 3.8 months (range, 0 to 30 months) and had a mean weight loss of 5.8 kg (range, 0 to 22 kg). The tumors ranged from 1 to 14 cm in length and averaged 4.7 cm. Preoperative chemotherapy and radiation therapy were administered in 11 patients (46%). Clinical staging suggested all patients were curable, and esophagectomy was performed in a transthoracic fashion in 27 (71%) and from a transhiatal approach in 11 (29%). Cervical anastomoses were undertaken in 16 patients (42%). The mean blood loss was 1,165 mL and ranged from 500 to 4,000 mL. The mean number of transfused units was 2.3 (range 0 to 8 U). Overall operative mortality was 18% (7 of 38). Major morbidity included pneumonia in 11 (29%), anastomotic leak in 4 (11%), chylothorax in 4 (11%), pulmonary embolus in 3 (8%), and stroke and myocardial infarction in 1 patient each (3%). Three patients have been cured of their esophageal cancer with survivals of 65, 70, and 72 months and an additional 7 patients are still alive. Three patients (8%) have been lost to follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Outcome after failed initial therapy for rupture of the esophagus or intrathoracic stomach.

Survival after rupture of the esophagus or intrathoracic stomach is improving, but continued leakage after initial therapy remains a problem. We retrospectively reviewed patients with rupture of the esophagus or intrathoracic stomach to determine the prevalence of continued leakage after initial therapy and how this complication affects outcome. Our review included 58 patients, 38 (66%) of whom had preexisting esophageal disease. The etiology of perforation was spontaneous rupture in 17, penetrating trauma in four, and iatrogenic injury in 35; two patients had perforation from other causes. Initial therapy consisted of drainage in eight, primary repair in 24, resection in 18, bypass in two, and observation in six. The overall mortality rate was 12% (7 of 58 patients) and continuing leaks were identified in 21% (12 of 58 patients). These leaks were unrelated to patient age, existence of prior disease, or delay in therapy but were more common after initial treatment by primary repair with or without pleural flap coverage compared to other management strategies (6 of 9 vs. 6 of 49; P < 0.001). Salvage therapy with survival was possible in 10 (83%) of 12 patients by means of esophagectomy in four, exclusion in one, drainage in two, or observation in three. Continuing leaks can be avoided by providing soft tissue coverage other than pleura over a primary repair and by not leaving an intrathoracic esophageal stump. Aggressive management of continuing leaks results in survival in more than 80% of patients.

Current results of therapy for esophageal perforation.

BACKGROUND: Prior reviews of esophageal perforation with delayed recognition have reported mortality rates as high as 66%. We performed a retrospective review of patients with nonmalignant esophageal perforation to assess the outcome of current management techniques. PATIENTS AND METHODS: Charts were reviewed of all patients who were treated for nonmalignant esophageal perforation between 1980 and 1993. They were 23 men and 10 women, mean age 49 +/- 3 years, 19 of whom were diagnosed early (< or = 24 hours) and 14 of whom were diagnosed late (> 24 hours). RESULTS: Perforations were due to instrumentation (16), operative injury (7), spontaneous rupture (4), trauma (4), and other causes (2). Pre-existing esophageal disease was identified in 23 patients (70%), including achalasia (9), stricture (7), varices (5), and other (2). Treatment included closure and fundoplication or muscle wrap (10), closure with or without pleural flap (7), resection only (7), resection and reconstruction (3), drainage only (4), and observation (2). Nonfatal complications included empyema (4), arrhythmia (3), persistent leak following attempted closure (2), and other (5). They occurred in 50% of both the early and late diagnosis groups and were of comparable severity in both. The overall mortality was 9% (3/33). Causes of death were sepsis (1) and multisystem organ failure (2). Mortality was 5% (1/19) in patients diagnosed early and 14% (2/14) of those diagnosed late. CONCLUSIONS: Current mortality rates in nonmalignant esophageal perforation are improved compared to previously published rates of 19% for all patients with the condition, 9% following early and 29% following late diagnosis (47 patients overall). We conclude that, despite a high incidence of associated complications, the survival rate following nonmalignant esophageal perforation is improving and the impact of delayed recognition is decreasing.

Neurogenic tumors of the mediastinum.

Neurogenic tumors can arise from neural cells in any location; however, they commonly are found in the mediastinum and, more specifically, most often are located in the posterior compartment. Neurogenic tumors can be benign or malignant, with a wide array of both clinical and pathologic features that are commonly classified by the cell type of origin. These tumors are usually detected on routine chest radiograph, and a computed tomographic scan is required to obtain more information about involvement of local structures. A magnetic resonance imaging scan may be necessary if a dumbbell-shaped component is identified or suspected. Treatment options vary depending on the presentation, but most often surgical resection is recommended. Whereas patients with benign neurogenic tumors have an excellent prognosis with complete surgical resection, patients with malignant neurogenic tumors still have poor long-term survival prospects.

Characterization of contractile properties of porcine mesenteric and tracheobronchial lymphatic smooth muscle.

We performed morphometric and length-tension analyses comparing mesenteric and tracheobronchial lymph vessel segments to determine the potential of the latter tissue to regulate pulmonary and mediastinal lymph flow via alterations in smooth muscle tone. Fresh porcine lymph vessel rings were prepared for 1) in vitro assessment of length-tension relationships and 2) histologic preparation and measurement of smooth muscle cross-sectional area (SMA). Mesenteric and tracheobronchial optimal vessel ring lengths were 3.1 +/- 0.2 and 3.5 +/- 0.2 mm, and maximum active tensions were 1518 +/- 25 and 1703 +/- 162 mg. Smooth muscle formed indistinct layers in each tissue, and only 30% of the smooth muscle was oriented circumferentially. Stress generated by the circular smooth muscle was similar to that generated by other types of vascular smooth muscle. In 75% of mesenteric vessel rings spontaneous contractions were observed that had a mean contraction frequency of 1.7 +/- 0.2 min-1 and a mean contraction amplitude of 349 +/- 35 mg, while only 40% of tracheobronchial vessels exhibited spontaneous contractions (p < 0.001) that had a mean frequency of 0.6 +/- 0.2 min-1 (p = 0.0021) and a mean contraction amplitude of 118 +/- 10 mg (p < 0.0001). We conclude that tracheobronchial lymphatic vascular smooth muscle is capable of developing stress similar to that generated by mesenteric lymph vessels, and that spontaneous rhythmic contractile activity is qualitatively and quantitatively different in tracheobronchial than in mesenteric porcine lymph vessels. The data suggest that tracheobronchial lymph vessels are capable of regulating pulmonary and mediastinal lymph flow through intrinsic mechanisms. Such regulation may occur by alterations in vascular resistance rather than via spontaneous pumping activity.

Anatomy of a disease management program.

Learn the strategies and planning behind disease management programs. Initiation and success depend on nurse leaders, case managers, and information technology.

Pursuing performance. New specs for ambulances and fleet managers.

It seems so easy. A call comes in, you get in the ambulance, strap on the seatbelt and turn the key. But there's much more that goes into building the hunk of metal you're sitting in. Each part must meet a design or performance specification. But who sets up these specifications and why? Is it all geared to help you get your patient to the hospital quickly but safely? And what challenges await the maintenance person who must keep that hunk of metal running--and running well? This article will answer some of those questions, but we hope it prompts you to ask even more.